Information regarding respiratory function of a living organism is important in the field of medicine. Respiratory function provides a measure of how efficiently air is moved through the respiratory system, and thus provides important clinical information for the diagnosis and treatment of many respiratory conditions and diseases. Some examples of these conditions are chronic obstructive pulmonary disease (COPD), asthma, and emphysema. In addition, respiratory function measurements allow medical practitioners to observe effects of a bronchodilator or long-term treatments for COPD, or conversely, the airway responses to a bronchoconstrictor challenge for assessment of airway reactivity.
Respiratory function testing includes mechanical function tests which typically compare the effort or driving pressure put forth by the organisms to some quantifiable outcome, such as the output of flow or minute ventilation. Lung function tests differ based on how these inputs and outputs are assessed. Examples of inputs to the respiratory system that are measured, include diaphragmatic electromyographic activity, changes in thoracic esophageal pressure or pleural pressure, changes in airway pressures in ventilated subjects, or noninvasive measures of drive including respiratory inductance plethysmography or impedance plethysmography, and whole body plethysmography. Examples of output measurements include flow, tidal volume, or ventilation measurements using devices that collect: flow at the airway opening. In general, the mechanical function of the respiratory system is best described by combining some measure of drive with output. Variables such as resistance and compliance can then be derived to assess the level of airway obstruction or loss of lung elasticity, respectively. This is the basis for classical physiologic modeling of the respiratory system: the comparison of transpulmonary pressure changes with flow or tidal volume, carefully assessed in the same time domain with avoidance of phase lag between signals.
Classical physiologic modeling measures total pulmonary resistance, dynamic compliance and related variables. However, the classical physiologic modeling relies on the invasive passage of an esophageal balloon for example, for measuring driving pressure, and flow as a measure of output. An esophageal balloon catheter is positioned in the midthoracic esophagus. Thus, classical physiologic measures are not used because of the invasive nature of the esophageal balloon catheter and the difficulty in calibrating the classical system under field conditions.
Lung function tests have evolved with respect to the sensors, recording devices, and analysis techniques used to evaluate input and output. However, a need still exists for the noninvasive determination of lung mechanical function and monitoring in human and animal subjects for clinical and research purposes. In this respect, a number of technologies to measure drive, mentioned above, are available. Devices such as single and double plethysmographs are used to measure drive. In the double chamber plethysmograph, thoracic and nasal flows are recorded as separate signals, whereas in barometric plethysmography, a single signal is recorded that is the net signal from the thoracic and nasal components. The latter is achieved simply on the basis that animals breathe inside a box where pressure changes are the net effects of both components. The aforementioned plethysmographic techniques, due to their size and complexity, preclude their use as a portable field test. In addition, these techniques enclose the subject, which is objectionable to both humans and animals.
Extending lung function tests to animals has been difficult because technological limitations prevent restraining a conscious animal for prolonged periods of time in devices or chambers such as, without limitations in plethysmograph chambers. As a result, most lung function studies to date have been limited to animals which are typically anesthetized or conscious animals that provide data with artifacts such as motion artifacts.
Significant challenges remain in conducting lung function tests in conscious animals. The respiratory system of conscious animals, such as canines, is evaluated by physical examination, x-rays, endoscopy, cytology, arterial blood gases, capnography and oximetry. Fluoroscopy can also be used for imaging the respiratory system in small animals, but only if they are sufficiently sedated. Simple measurements of spirometry using a facemask have been conducted in small animals that provide measurements of flow, tidal volume, minute ventilation, and respiratory frequency. These measurements are generally not useful beyond clinical impressions. None of these currently used methods address the mechanical function of the lungs. At best, the current methods determine tidal volume, airflow resistance, lung elasticity, and diffusion characteristics. Some of these characteristics can be inferred indirectly such as, for example, lung volume using an x-ray, and diffusion based on arterial blood gases or capnography, but are typically inaccurate measures.
A need still exists for improved systems and methods which provide for measuring respiratory function for health care practitioners, are portable and which are non-invasive to the living organisms. Further, there is still a need for pulmonary function testing devices for conscious animals.
The present invention relates to a system for measuring respiratory function of living organisms such as measuring airway obstruction, airway reactivity and changes in lung volume. In a preferred embodiment, the system for measuring respiratory function includes measuring gas compression or expansion which is the difference between the effort (defined herein as having active and passive work components and change in lung volume) required to breathe and airflow, by the combination of external sensors and direct measures of true flow. A preferred embodiment of the system of the present invention uses a direct comparison of an external flow signal (EFS) indicative of effort required to breathe which includes both an active work component and a passive work component indicative of the passive recoil of the lung, diaphragm and chest wall during exhalation, and the uncompressed flow, preferably in the same time domain, thereby permitting real time analysis using a plurality of measured variables to assess respiratory function. The apparatus and methods of the present invention provide non-invasive measures of airway obstruction or respiration restriction in the subjects.
The present invention is important for patients/subjects with known clinical obstructions. Response to treatments such as bronchodilators can be monitored and assessed to measure improvements using the present invention.
In addition, it is important to measure respiratory function in subjects who have a subclinical form of an airway obstruction, i.e., the subjects who do not normally display the clinical symptoms associated with airway obstructions. The present invention provides diagnosis of subclinical progressive or episodic conditions by testing the airway reactivity of the subjects. This is accomplished by provoking an obstruction of the airways by challenging the airways with a chemical such as a histamine, for example, and using the present invention to measure changes in the respiratory function of the subject.
According to one aspect of the present invention, the methods for measuring respiratory function of the present invention include the steps of obtaining a signal indicative of the effort required to breathe by the living organism, obtaining a signal indicative of uncompressed airflow through the respiratory system of the subject as measured at the airway opening, processing the signals indicative of effort and flow by comparing the signals dynamically in the same time domain to detect transient periods of gas compression or expansion that signify airway obstruction and to provide a signal indicative of the respiration restriction of the subject. Increase in respiratory system impedance is therefore detected by measuring gas compression or expansion indirectly, using non-invasive sensors.
A preferred embodiment of the present invention to measure airway reactivity features obtaining a signal indicative of the effort required to breathe and also referred to herein as the external flow sensor (EFS), obtaining a signal indicative of airflow through the respiration system of the subject and processing the two signals which includes the comparison of the two signals to provide a signal indicative of the measure of respiration restriction of the subject. This method uses bronchoconstrictors to challenge the respiratory system of the subjects so as to provoke a response and test the airway reactivity of the subjects.
The preferred embodiment to measure airway reactivity may employ different sensors such as respiration induction plethysmography or impedance plethysmography or devices such as piezoelectric sensors to obtain the signal indicative of effort required to breathe. Fiber optic respiratory plethysmography methods may also be used similar to respiratory inductance plethysmography. The bands in the fiber optic embodiment are composed of fiber optic material. The signal indicative of effort or change in lung volume can also be obtained by using optoelectronic plethysmography that measures the movement of a plurality of retro-reflective markers using television cameras connected to a motion analyzer. The signal indicative of uncompressed airflow through the respiratory system can be obtained through the use of a pneumotachographic measurement device, an ultrasonic device, a thermistor or a breath-sound intensity device. Additionally, the signal indicative of the effort required to breathe is calibrated by assigning a voltage span to the specific volume or flow span. Calibration for the signal indicative of uncompressed airflow is optional, but preferred in conjunction with the use of methods such as flow meters or precision volume syringes.
The signals indicative of the effort and airflow are amplified and digitized. The signals are then compared and subtracted to give an indication of the respiration function of the subject. A programmable computer can be programmed to perform an analysis of the measured signals and a display formatted to show the recorded and processed data. An electronic memory can be used to store the measured and/or processed data. The comparison of the effort or external flow signal with uncompressed airflow is performed either by overlapping the waveforms and performing visual comparisons between the two waveforms or by synthesizing a composite waveform by performing a digital subtraction point-by-point of the airflow from the external flow or effort signal. Further, Fourier analysis may be used to compare the signal indicative of effort with uncompressed airflow. For a subject with a healthy respiration system, the effort and flow signals are in phase. However, during a condition such as one that occurs with bronchoconstriction, the airflow signal of the subject is no longer in phase with the signal indicative of effort or thoracic movement. During the condition when the airways are obstructed the effort signal or thoracic movement will lead nasal flow. This phase shift occurs in the time domain. The magnitude of the phase shift can be used as a measure of airway resistance or obstruction.
Another preferred embodiment of the present invention to measure clinical obstructions and response to treatments, such as the administration of bronchodilation medication, features obtaining a signal indicative of the effort required to breathe and a signal indicative of airflow through the respiration system and processing the two signals to obtain a signal indicative any respiration restriction of the subject. In another embodiment, the present invention can be used as a monitoring system for respiration functions. The advantage of the present invention in terms of its lack of obtrusiveness allows the subject to adopt normal body posture and yet be monitored. The monitoring application of the present invention is well suited for continuous or intermittent home or hospital monitoring of adults, children, infants and animal subjects. In particular, for patients on continuous positive airway pressure (CPAP) or assisted ventilation, the system of the present invention can be coupled to a CPAP delivery device or ventilator. The present invention triggers the use of the ventilators upon detecting respiratory restriction. Similarly, an oxygen delivery system can be coupled to the respiration function measurement system of the present invention.
According to another aspect of the present invention, an apparatus for obtaining a signal indicative of respiration of a living organism includes a first device that obtains a first input signal indicative of effort required to breathe by the organism, a second device that obtains a second input signal indicative of actual airflow through the respiratory system of the organism and a processing device that processes the first and second inputs to form a third signal indicative of respiration restriction of the organism. The processing device may be a programmable computer, programmed to perform an analysis of the measured input signals and a display formatted to show the recorded and processed data. The processing device can process the input signals using analog circuitry or digital circuitry. An electronic memory can be used to store the measured and/or processed data. The programmable computer can be a laptop computer, facilitating the portability of the apparatus. Thus, the system for measuring respiration function is lightweight and compact, having a weight of less than fifteen (15) pounds, preferably less than ten (10) pounds. This provides a portable system that can be readily transported by the user.
According to another aspect of the present invention, an apparatus and method of a preferred embodiment measures lung function and structure during tidal breathing or during occlusions for conscious animals. The method for measuring airway and lung tissue functionality includes calibrating a chamber that is a constant volume plethysmograph in which the subject""s head is positioned outside the chamber but the subject breathes into the chamber. The calibration may include adjusting the gain settings of amplifiers, and calibrating the chamber pressure relative to a known volume of gas. The method to measure lung functionality further includes acclimatizing a subject in the chamber, measuring the functional residual capacity (FRC) of the subject and the airway pressure as it relates to chamber pressure. A movable cover or shutter assembly is preferably closed prior to the FRC measurement. Upon opening the shutter assembly airway resistance is measured. The method may further include the measurement of dynamic flow metric indices which provide the ability to study differences between inspiratory and expiratory breaths.
The foregoing and other objects, features and advantages of the invention will be apparent from the following more particular description of preferred embodiments of the invention, as illustrated in the accompanying drawings in which like reference characters refer to the same parts throughout the different views. The drawings are not necessarily to scale, emphasis instead being placed upon illustrating the principles of the invention. The principles and features of this invention may be employed in varied and numerous embodiments without departing from the scope of the invention.